Department of Internal Medicine and Public Health, University of L'Aquila, Viale S. Salvatore, Delta 6 Medicina, 67100 Coppito - L'Aquila, Italy.
Curr Pharm Biotechnol. 2011 Sep;12(9):1343-53. doi: 10.2174/138920111798281018.
The vascular endothelium plays a pivotal role in the maintenance of vessel wall integrity. In this regard, endothelial cells actively regulate vascular reactivity by responding to mechanical forces and neurohormonal mediators by releasing a variety of relaxing and contracting factors. Nitric oxide (NO), an endogenous gas synthesized by NO synthases (NOSs) is the main endothelium-derived vasodilator. Continuous production of NO by constitutive NOS maintains the vasculature in a state of vasodilation, whereas its phasic generation by inducible NOS can acutely dilate an artery in response to either physiological or pathological stimuli. Under homeostatic conditions, the endothelium maintains normal vascular tone and blood flow, and there is little or no expression of proinflammatory factors. However, both traditional and novel cardiovascular risk factors initiate a chronic inflammatory process that is accompanied by a loss of vasodilator and antithrombotic factors and an increase in vasoconstrictor and prothrombotic products. Furthermore, increased oxidative stress may result in a complete derangement of the NO system, with decreased NO bioavailability and a paradoxical NOS-related oxidant generation. Because of the antiatherogenic, antithrombotic properties of NO and the proatherogenic prothrombotic actions of endogenous oxidants, a decreased NO bioavailability with increased oxidative stress will result not only in impaired endothelium-dependent vasorelaxation but also in the acceleration of atherogenesis and onset of acute atherotrombotic events. The concepts of "endothelial dysfunction" and "endothelial activation" referring to different alterations in endothelial phenotype, may contribute to the development and clinical expression of atherosclerosis.
血管内皮在维持血管壁完整性方面起着关键作用。在这方面，内皮细胞通过释放各种舒张和收缩因子来响应机械力和神经激素介质，从而积极调节血管反应性。一氧化氮（NO）是由一氧化氮合酶（NOS）合成的内源性气体，是主要的内皮衍生血管舒张因子。组成型 NOS 持续产生的 NO 使血管保持舒张状态，而诱导型 NOS 产生的 NO 相可以在生理或病理刺激下迅速扩张动脉。在稳态条件下，内皮维持正常的血管张力和血流，几乎没有或没有炎症因子的表达。然而，传统和新型心血管危险因素会引发慢性炎症过程，伴随着血管舒张和抗血栓因子的丧失以及血管收缩和促血栓因子的增加。此外，氧化应激的增加可能导致 NO 系统的完全紊乱，NO 的生物利用度降低，NOS 相关的氧化剂生成增加。由于 NO 具有抗动脉粥样硬化、抗血栓形成的特性，而内源性氧化剂具有促动脉粥样硬化、促血栓形成的作用，因此 NO 生物利用度降低伴氧化应激增加不仅会导致内皮依赖性血管舒张功能受损，还会加速动脉粥样硬化的发生和急性动脉血栓形成事件的发生。“内皮功能障碍”和“内皮激活”的概念指的是内皮表型的不同改变，可能有助于动脉粥样硬化的发展和临床表达。
